Epilepsy with migrating focal seizures
Barcia, Giulia (Universitat Autònoma de Barcelona)
Chemaly, Nicole (Universitat Autònoma de Barcelona)
Kuchenbuch, Mathieu (Universitat Autònoma de Barcelona)
Eisermann, Monika (Universitat Autònoma de Barcelona)
Gobin-Limballe, Stéphanie (Universitat Autònoma de Barcelona)
Ciorna, Viorica (Universitat Autònoma de Barcelona)
Macaya Ruiz, Alfons (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Lambert, Laetitia (Universitat Autònoma de Barcelona)
Dubois, Fanny (Universitat Autònoma de Barcelona)
Doummar, Diane (Universitat Autònoma de Barcelona)
Billette de Villemeur, Thierry (Universitat Autònoma de Barcelona)
Villeneuve, Nathalie (Universitat Autònoma de Barcelona)
Barthez, Marie-Anne (Universitat Autònoma de Barcelona)
Nava, Caroline (Universitat Autònoma de Barcelona)
Boddaert, Nathalie (Universitat Autònoma de Barcelona)
Kaminska, Anna (Universitat Autònoma de Barcelona)
Bahi-Buisson, Nadia (Universitat Autònoma de Barcelona)
Milh, Mathieu (Universitat Autònoma de Barcelona)
Auvin, Stéphane (Universitat Autònoma de Barcelona)
Bonnefont, Jean-Paul (Universitat Autònoma de Barcelona)
Nabbout, Rima (Universitat Autònoma de Barcelona)
Universitat Autònoma de Barcelona. Departament de Pediatria, Obstetrícia i Ginecologia i de Medicina Preventiva i Salut Pública

Date:	2019
Abstract:	To report new sporadic cases and 1 family with epilepsy of infancy with migrating focal seizures (EIMFSs) due to KCNT1 gain-of-function and to assess therapies' efficacy including quinidine. We reviewed the clinical, EEG, and molecular data of 17 new patients with EIMFS and KCNT1 mutations, in collaboration with the network of the French reference center for rare epilepsies. The mean seizure onset age was 1 month (range: 1 hour to 4 months), and all children had focal motor seizures with autonomic signs and migrating ictal pattern on EEG. Three children also had infantile spasms and hypsarrhythmia. The identified KCNT1 variants clustered as "hot spots" on the C-terminal domain, and all mutations occurred de novo except the p. R398Q mutation inherited from the father with nocturnal frontal lobe epilepsy, present in 2 paternal uncles, one being asymptomatic and the other with single tonic-clonic seizure. In 1 patient with EIMFS, we identified the p. R1106Q mutation associated with Brugada syndrome and saw no abnormality in cardiac rhythm. Quinidine was well tolerated when administered to 2 and 4-year-old patients but did not reduce seizure frequency. The majority of the KCNT1 mutations appear to cluster in hot spots essential for the channel activity. A same mutation can be linked to a spectrum of conditions ranging from EMFSI to asymptomatic carrier, even in the same family. None of the antiepileptic therapies displayed clinical efficacy, including quinidine in 2 patients.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	Neurology: Genetics, Vol. 5 (october 2019) , ISSN 2376-7839

DOI: 10.1212/NXG.0000000000000363
PMID: 31872048

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